The cellular prostaglandin interaction with angiotensin and kinins has been considered of great importance in the regulation of systemic blood pressure and possibly in local regulation of the brain microcirculation. Therefore, we investigated the effect of angiotensin (I or II) or bradykinin on prostaglandin synthesis in separately cultured cerebrovascular endothelium and smooth muscle, and compared their responses to that in the glia. The synthesis of PGI2 was measured indirectly in the medium of each cell type using radioimmunoassay with (125I) 6-keto-PGF1Alpha. The greatest stimulation of prostaglandin release was observed in the medium of the smooth muscle cells exposed to either angiotensin (I or II) or to bradykinin. (The concentrations of 6-keto-PGF1Alpha were up to 100 times over the basal levels). The synthesis of prostaglandin in endothelium and glia was not significantly affected by the addition of angiotensin I. However, a slight enhancement of prostaglandin release from each cell line was observed after incubation with either angiotensin II or bradykinin (20-30% over basal level). These results strongly indicate that the cerebromicrovascular smooth muscle cells represent the most sensitive site for prostaglandin-peptide interaction which may be responsible for the modulation of vascular reactivity. The less responsive synthesis of prostaglandin to angiotensin and bradykinin observed in endothelium and glia suggests that these cells might serve as protectors of smooth muscle by inactivating peptides or by other mechanisms. Thus, each of the cells might have an influence on the cerebral microcirculation through its distinct and interrelated actions.